Natural killer cell cytotoxicity and its regulation by inhibitory receptors

Natural killer (NK) cells express an array of germ-line encoded receptors that are capable of triggering cytotoxicity. NK cells tend to express many members of a given family of signalling molecules. The presence of many activating receptors and many members of a given family of signalling molecules can enable NK cells to detect different kinds of target cells, and to mount different kinds of responses. This contributes also to the robustness of NK cells responses; cytotoxic functions of NK cells often remain unaffected in the absence of selected signalling molecules. NK cells express many MHC-I-specific inhibitory receptors. Signals from MHC-I-specific inhibitory receptors tightly control NK cell cytotoxicity and, paradoxically, maintain NK cells in a state of proper responsiveness. This review provides a brief overview of the events that underlie NK cell activation, and how signals from inhibitory receptors intercept NK cell activation to prevent inappropriate triggering of cytotoxicity.